The glaucomas are a group of complex neurodegenerative diseases. As a consequence of this neurodegeneration, glaucoma patients exhibit a loss of retinal ganglion cells (RGCs), characteristic changes in the visual field, and degeneration of the optic nerve (Ritch, R., et al. (1996)1, and Weinreb & Khaw, (2004)2. Glaucoma is traditionally viewed as a pressure-induced neurodegeneration, in which deleteriously high intraocular pressure (IOP) results in optic nerve damage over time. As a consequence, all major existing glaucoma therapeutics aim to lower IOP. However, many individuals who have high IOP for extended periods do not develop optic nerve and retinal damage, whereas others develop optic nerve damage despite normal IOP values (Heijl, A., et al. (2002)3, Collaborative Normal-Tension Glaucoma Study Group (1998)4. Thus, glaucoma is defined as a neurodegeneration and magnitude of IOP may not indicate current or future glaucoma status. Therefore, treatments that directly target the retina and optic nerve need to be developed.
Mouse studies are very useful for studying mechanisms contributing to multifactorial diseases and for testing potential treatments; see John, S. W., et al. (1999)5. DBA/2J mice are a naturally occurring mouse model of glaucoma. DBA/2J mice develop an age-related form of hereditary glaucoma initiated by mutations in two genes, Tyrp1 and Gpnmb; see John, S. W. M., Smith, et al. (1998)6, Chang, B., et al. (1999)7, and Anderson, M. G., et al. (2002)8. Clinically, indications of DBA/2J glaucoma are first evident by a pigment-dispersing iris disease that involves melanosomal and inflammatory components. As dispersed pigment from the iris disease accumulates within the aqueous humor drainage sites, DBA/2J mice develop an elevated IOP, which progressively insults RGCs and the optic nerve. By 10 to 12 months, the majority of DBA/2J mice have severe glaucoma evident by massive RGC loss and optic nerve damage.
Little is known about the mechanisms or molecular pathways that contribute to RGC degeneration in the glaucomas. As in other neurodegenerative diseases, the majority of effort has focused on apoptotic degeneration pathways; see Quigley, H. A. (1999)9, and Nickells, R. W. (2004)10. Recently, there has been recognition that distinct degenerative processes exist within different parts of a neuron, see Raff, M. C., et al. (2002)11.
Bone marrow transplantation combined with radiation or chemotherapy is used in the field of clinical oncology where it is used for Non-Hodgkins Lymphoma, Hodgkins Disease, breast cancer, and some types of leukemia and testicular cancer. Intense immunosuppressive conditioning combined with autologous hematopoietic stem cell transplantation is reported to treat autoimmune diseases such as multiple sclerosis (MS) and lupus, see Robert A. Good (July 2000)12.
The above review demonstrates a need continues to exist in the medical arts for more effective methods of treating and inhibiting the progression of neurodegeneration that accompanies the forms of glaucoma.